Juvenile Idiopathic Arthritis

Author(s): Todd R. Lefkowitz, MD , Sean Bemanian, MD

Originally published:11/10/2011

Last updated:04/21/2016

1. DISEASE/DISORDER:

Definition

Juvenile idiopathic arthritis (JIA), previously known as juvenile rheumatoid arthritis (JRA) is a form of arthritis (ie, swelling or limitation of a joint with warmth, pain or tenderness) of unknown etiology that occurs for at least 6 weeks in a child younger than 16 years of age, after other known conditions are excluded. It can continue into adulthood, causing significant disability.

Etiology

JIA appears to be influenced by both genetic and environmental factors. Twin and family studies strongly indicate a genetic component.  In addition to HLA associations, both cell mediated and humoral immunity play a role. Multiple genes relating to inflammation and immune regulation are believed to be involved.  There is evidence of autoimmune dysregulation, with positive antinuclear antibody (ANA) in 40% of patients. However, evidence from treatments designed to block the inflammatory cascade indicate that systemic inflammation may play a greater role.  Our understanding of the etiology of JIA continues to evolve.

Epidemiology including risk factors and primary prevention

JIA is one of the most common forms of arthritis in childhood. The prevalence is approximately 1 per 1000. Depending on subtype, girls may be more affected than boys.

Patho-anatomy/physiology

  • JIA is an inflammatory syndrome characterized by chronic synovial inflammation with B lymphocytes. Macrophage and T lymphocyte invasion occurs, along with cytokine release with further synovial proliferation. Eventually, the thickened synovium (pannus) contributes to joint destruction.
  • Subtypes (ILAR classification)
    • Oligoarticular
      • Most common (50%-60%), best prognosis
      • Fewer than four joints affected in first 6 months
      • Subdivided into persistent or extended oligoarthritis
      • Larger extremity joints, especially knees, most commonly affected
      • Iritis, especially in girls
    • Polyarticular
      • Occurs in 30%-35% of cases
      • More than five joints during the first 6 months
      • Symmetric involvement of small joints of hands and feet
      • Cervical spine and TMJ may be affected
      • Rheumatoid factor (RF) positive, variable prognosis, more aggressive disease course
      • RF negative, generally girls with symmetric small joint involvement and severe inflammation
    • Systemic
      • About 10% of cases
      • High spiking fevers for at least 2 weeks, quotidian pattern
      • Rash is evanescent, salmon colored, macular, accompanies fever
      • Arthritis occurs later, a month or longer
    • Other types (less common)
      • Psoriatic – Presence of asymmetric arthritis and psoriatic rash, if rash is absent, any two of the following, family history of psoriasis in a first degree relative, dactylitis, or nail pitting.
      • Enthesitis related – boys > 8 years old, enthesitis at the sites of tendon insertion onto bone, may involve sacroiliac joints, spine and acute iritis. Most are HLA-B27 positive, associated with ankylosing spondylitis, reactive arthritis, or inflammatory bowel disease-associated arthritis.
      • Undifferentiated – patients generally do not meet inclusion criteria for any other category or they may meet criteria for more than one subtype.

Disease progression including natural history, disease phases or stages, disease trajectory (clinical features and presentation over time)

  • New onset/acute:
    • Oligoarticular
      • Peak onset: pre-school age
      • Joint pain, swelling, tenderness, specially knees
    • Polyarticular
      • Age of peak onset:
        • RF positive: > 10 years
        • RF negative: 1-3 years
      • Pain, swelling, tenderness in greater than five joints
    • Systemic
      • No peak age of onset
      • Rash, daily fever for about 2 weeks
  • Subacute: Systemic presents with joint pain in the first six months. The other types may resolve in six months.
  • Chronic/stable: Oligoarticular JIA that lasts more than six months is characterized as “extended.” Complete remission can be expected in most patients. The rest continue to have symptoms into adulthood, with about 30% having significant disability.
  • Pre-terminal: Only in very severe cases, affecting cervical spine or causing significant debility

Specific secondary or associated conditions and complications

  • Anorexia, weight loss, growth failure
  • Cardiopulmonary involvement
  • Anemia
  • Decreased physical activity contributes to weakness, obesity (which increases load on joints)
  • Atlantoaxial instability associated with cervical spine involvement; increases risk of spinal cord injury
  • Concerns have been raised about increased rates of cancer (does not seem to be related to treatment with biologic agents as was once thought)
  • Uveitis, specifically iridocyclitis. More common in females affected with oligoarticular arthritis and in patients less than 6 years of age with a positive ANA. Usually asymptomatic, but if not diagnosed early may result in permanent blindness.
  • Growth disturbances including growth retardation and accelerated growth resulting in conditions such as leg length discrepancies
  • Pain is common early in disease course but diminishes as patients complete puberty
  • Micrognathia if TMJ arthritis disturbs the growth plate
  • Suppression of the immune system by disease modifying antirheumatic drugs (DMARDs) increases the risk of infections and malignancies
  • Osteopenia and osteoarthritis
  • Fractures
  • Macrophage Activation Syndrome (MAS) resulting from uncontrolled activation and proliferation of T lymphocytes and macrophages is a complication with systemic JIA; a life threatening condition resulting in persistent fever, pancytopenia, hepatosplenomegaly, and coagulopathy.

2. ESSENTIALS OF ASSESSMENT

History

  • Joint pain and swelling, often noted incidentally after trauma
  • Stiffness worse in morning or after naps, better later in the day
  • Persistence of symptoms; for at least six weeks in a six-month period
  • History of fever without other cause, in absence of joint symptoms, can be three days, with a double spike pattern of high temperatures
  • Child refusing to walk, or using hands to walk
  • Pain with ambulation, morning stiffness, “gelling” sensation (stiffness after a joint remains in one position for a prolonged period), joint swelling, and difficulty with buttons or writing.
  • Photophobia, pain, redness, headache, and visual changes.
  • Isolated musculoskeletal pain is generally not JIA.
  • Differential diagnoses include Perthes disease, slipped capital femoral epiphysis (SCFE), malignancy (osteosarcoma for joint pain, leukemia for fever combined with joint pain), ankylosing spondylitis, inflammatory bowel disease, septic arthritis.

Physical examination

  • Painful, swollen joints
  • Number of joints
    • < 5: Oligoarticular
    • > 5: Polyarticular
  • Knees, wrists and ankles in polyarticular
  • Any joint can be affected, including small joints of the fingers, sternocostal, spinal (including cervical), and jaw.
  • Decreased range of motion, flexibility
  • Check eyes for uveitis in girls with positive ANA and oligoarticular JIA
  • Systemic‑may have splenomegaly, lymphadenopathy, rashes
  • Cardiac exam‑may have pericarditis, myocarditis
  • Receding chin from early ossification of the mandible (micrognathia)
  • Leg length discrepancy
  • Gait‑antalgic limp

Functional assessment

  • Childhood Health Assessment Questionnaire (CHAQ, Disability Scale‑measures ADL independence)
  • Juvenile Arthritis Self-Report Index‑measures self-care, mobility, school and extracurricular involvement
  • Juvenile Arthritis Functional Assessment Report (JAFAR)‑focuses on performance of physical tasks, has parental and self report versions

Laboratory studies

No specific laboratory studies definitely diagnose JIA.

  • RF‑positive 3%-5% in polyarticular subtype
  • ANA positive in 80% of oligoarticular subtype, associated with uveitis
  • Serial trending of erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) help gauge effectiveness of treatment
  • CBC to evaluate anemia of chronic disease and leukocytosis
  • Joint aspiration to rule-out septic arthritis

Imaging

  • Plain films, magnetic resonance imaging (MRI), ultrasound used to detect joint changes
  • Periarticular soft tissue swelling, overgrown or ballooned epiphyses, periostitis
  • Later‑erosive disease, joint space loss.
  • MRI has high sensitivity to detect bone damage
  • Ultrasound useful for assessing number of joints involved and differentiating between tendon and articular involvement
  • Useful to rule out other causes of joint pain and swelling
  • Dual-energy x-ray absorptiometry (DEXA)‑osteoporosis is a common problem

Supplemental assessment tools

  • Physician and parent global assessments of overall disease activity
  • Steinbrocker functional classification

Early predictions of outcomes

  • Poorer prognosis associated with hip or cervical spine involvement, joint space erosion, positive RF
  • Systemic and polyarthritis with RF positivity have the highest incidence of advanced joint damage and long term disability
  • Early intensive therapy in JIA may improve long term disease outcomes, including prevention of cumulative joint damage

Environmental

  • More severe cases may require home modifications, including ramps and roll-in showers secondary to mobility limitations
  • Changing doorknobs to handles may help those with advanced hand and wrist involvement
  • School accommodations based on Section 504 of the Rehabilitation Act
    • Regulations to accommodate decreased ability to get from class to class, take notes, or carry books

Social role and social support system

  • Isolation, depression, poor self-esteem‑debated in literature
  • Family frustration due to delay of diagnosis in some cases
  • Pain leads to missed school and participation

Professional Issues

Physicians must ensure they educate patients on their disease course, as many children are eager to learn about their prognosis and functional limitations. Physiatrists must be strong patient advocates in multiple settings, including school, home, and community environments. Sensitivity to patients’ cultural background, ethnicity, gender, age, religious beliefs, and sexual orientation is paramount to building trust across the spectrum of care. Patient safety issues include minimizing medical errors, addressing medication side effects, and providing a safe environment at home and during therapy.

3. REHABILITATION MANAGEMENT AND TREATMENTS

Available or current treatment guidelines

  • 2013 Update of the 2011 American College of Rheumatology Recommendations for the Treatment of Juvenile Idiopathic Arthritis
  • American College of Rheumatology 2011 guidelines for therapeutic agents 1,2
  • Exercise and Physical Activity Conference Arthritis Working Group 2002 Guidelines3

At different disease stages

New onset/acute

  • Includes symptom relief:
    • Non-steroidal anti-inflammatory drugs (NSAIDs) for pain and decrease of inflammation include:
      • Diclofenac
      • Naproxen
      • Ibuprofen
      • Indomethacin
      • Meloxicam
    • Intra-articular steroid injections with triamcinolone hexacetonide is preferred for children
  • Includes rehabilitation strategies that stabilize or optimize function or prepare for further interventions at later disease stages:
    • Gentle range of motion
    • Cold packs applied to joints
    • Supportive orthoses, especially knees and wrists to maintain alignment
    • Shoe modifications to support ankles and feet
    • Appropriate rest from activities during flares

Subacute

  • Includes secondary prevention and disease management strategies:
    • Prednisone for acute exacerbations
    • DMARDs such as methotrexate, leflunomide, sulfasalazine combined with an NSAID
    • Anti–interleukin (IL)-1 agents include anakinra, canakinumab, rilonacept
    • Anti–IL-6 agent tocilizumab
    • TNF- α inhibitors like etanercept, infliximab, and adalimumab help reduce flare-ups
      • Repeated annual screening of TB in low risk patients with a negative initial TB screen is not recommended
    • Anti-tumor necrosis factor drugs in addition to those above
      • May have severe adverse effects, requiring dose adjustments.
  • Includes rehabilitation strategies to optimize function:
    • Range of motion
    • Heat, including paraffin and beads for hands
    • Hydrotherapy
    • Ultrasound generally avoided in children due to controversy over growth plates
    • Mobilization to prevent debility
    • Joint protection techniques
    • Adaptive equipment for mobility (walker with forearm supports if grip is too difficult) and ADL (adapted silverware, pencil or crayons)
    • Adapted computer access

Chronic/stable

  • Includes secondary prevention and disease management strategies;
    • Monitor cervical spine
    • Supportive orthotics, especially for knees, feet, ankles and wrists
    • Jaw guards for sport if jaw involved
  • Includes palliative strategies
    • Supportive nutrition
  • Includes symptom relief:
    • NSAIDs
    • Complementary and alternative medicine techniques common
  • Includes rehabilitation strategies to optimize function
    • Massage
    • Stretching and flexibility
    • Yoga
    • Exercise program including aquatics
      • Aerobics, while protecting joints
      • Strengthening, isometrics may be better for affected joints
    • Participation in sports is not contraindicated
    • Joint protection strategies
    • Environmental adaptations
    • Nighttime resting splints

Pre-terminal or end of life care:

  • Severe complications, such as cervical spine involvement can lead to severe disability and early death.
  • Includes symptom relief:
    • Continued pain relief and supportive care

Coordination of care

A multidisciplinary team is needed to properly care for patients with JIA. Medical teams commonly include a pediatric rheumatologist, physiatrist, orthopedic surgeon for deformities (ie, avascular necrosis of the femoral neck), and ophthalmologists. Physical and occupational therapists can address joint ROM, pain, strength, and endurance. Occupational therapists may also assist with school and environmental modifications. Vocational therapists can address education and employment plans after high school and college. Psychologists and social workers may assist with coping strategies, self-esteem, and transition into adulthood.

Patient & Family Education

  • Joint protection
  • Energy conservation techniques
  • Need for regular range of motion
  • Need for maintaining overall health, including nutrition and fitness
  • Adequately explain pain regimen and any potential adverse effects.
  • Educate on activity restrictions and therapy programs.
  • Patients and families should be aware of complications of various treatments. Medical complications include MAS; atlantoaxial involvement which precludes participation in contact sports, as well as gymnastics and jumping on trampolines, due to risk of subluxation/dislocation causing spinal cord injury.
  • Weight bearing status, recommended medical, surgical, and rehabilitative treatments; and duration of treatment.

Emerging/unique Interventions

IMPAIRMENT-BASED MEASUREMENT

  • Measures of joint erosion and loss of joint space (percent)
  • Childhood Health Assessment Questionnaire (Discomfort scale)
  • JADAS (Juvenile Arthritis Disease Activity Score)

MEASUREMENT OF PATIENT OUTCOMES

  • Juvenile Arthritis Quality of Life Questionnaire physical function and emotional well being
  • Childhood Arthritis Health Profile physical and psychosocial functioning, and family impact of the disease
  • Quality of My Life Questionnaire focuses on separating problems related to JIA versus other issues
  • Childhood Health Questionnaire general health, pain, physical activity, self esteem and family issues
  • Pediatric Quality of Life Inventory Scales physical, emotional, social, school function

Translation into practice: Practice “pearls”/performance improvement in practice (PIPs)/changes in clinical practice behaviors and skills

  • Leg length discrepancy related to joint damage due to chronic synovitisof involved lower extremity joint may require orthotic adjustments, including shoe lifts.
  • Symptom management with intra-articular steroids can decrease inflammation and help prevent synovial overgrowth.
  • Exercise should be promoted, even in times of disease flare. Regular low to high intensity exercise, including aquatic therapy, has been shown to decrease pain, improve clinical symptoms and quality of life.

4. CUTTING EDGE/EMERGING AND UNIQUE CONCEPTS AND PRACTICE

Cutting edge concepts and practice

Autologous stem cell transplants are reserved for those who have failed prior therapy

5. GAPS IN THE EVIDENCE-BASED KNOWLEDGE

Gaps in the evidence-based knowledge

DMARDs have revolutionized the treatment of JIA, improving the quality of life for patients with joint-related disability. Since these drugs are fairly new to the market, however, the long term consequences remain unknown.  Since many children with JIA continue to have disease as adults, patients may remain on these agents for decades, necessitating further investigation into their long term effects.

REFERENCES

  1. Eustice C. 2011 ACR Recommendations for the treatment of juvenile idiopathic arthritis. (Updated April 2011). International League of Associations for Rheumatology (ILAR). http//:www.about.com/Guide. Accessed June 6, 2011.
  2. Beukelman T, Patkar NM, Saag KG et al. 2011 American College of Rheumatology recommendations for the treatment of juvenile idiopathic arthritis: initiation and safety monitoring of therapeutic agents for the treatment of arthritis and systemic features. Arthritis Care Res. 2011;63:465-482.
  3. Yelin EH, Dunlop D, Jette AM. Work group recommendations: 2002 Exercise and Physical Activity Conference, St. Louis, Missouri/Session 1. Arthritis and disability: impact and consequences. American College of Rheumatology. Arthritis Care Res. 2003;49(1):121. http://onlinelibrary.wiley.com/doi.1002/art.544/abstract. Accessed June 6, 2011.
  4. Duffy CM: Measure of health status, functional status, and quality of life in children with juvenile idiopathic arthritis: clinical science for the pediatrician. Rheum Dis Clin N Am. 2007; 33:389-402.
  5. Martini A, Lovell DJ; Juvenile idiopathic arthritis: state of the art and future perspectives. Ann Rheum Dis. 2010;69:1260-1263.
  6. Philpott J, Houghton K, Luke A: Physical activity recommendations for children with specific chronic health conditions: juvenile idiopathic arthritis, hemophilia, asthma and cystic fibrosis. Paediatr Child
  7. Weiss JE, Ilowite NT: Juvenile idiopathic arthritis. Rheum Dis Clin N Am. 2007;33:441-470.
  8. Espinosa M, Gottlieb B: Juvenile Idiopathic Arthritis. Pediatrics in Review. 2012; 33(7): 303-313
  9. Srinivasan R, Hacker C, Cubillos N. Juvenile Idiopathic Arthritis.  In: Cristian A, Batmangelich S, eds. Physical Medicine and Rehabilitation Patient Centered Care: Mastering the Competencies. 1st edition Demos Medical; September 4, 2014; Chapter 31: p 353-364
  10. Stoll ML, Cron RQ. Treatment of juvenile idiopathic arthritis: a revolution in care. Pediatric Rheumatology. 2014;12:13.
  11. Limenis E, Grosbein HA, Feldman BM. The Relationship Between Physical Activity Levels and Pain in Children with Juvenile Idiopathic Arthritis. Journal of Rheumatology. 2014; 41: 345-351
  12. Hinze C, Gohar F, Foell D. Management of juvenile idiopathic arthritis: hitting the target. Nature Review Rheumatology. 2015; 11:290–300.
  13. Ringold S, Weiss PF, Beukelman T, DeWitt EM, Ilowite NT, Kimura Y, et al. 2013 update of the 2011 American College of Rheumatology recommendations for the treatment of juvenile idiopathic arthritis: recommendations for the medical therapy of children with systemic juvenile idiopathic arthritis and tuberculosis screening among children receiving biologic medications. Arthritis Rheum. 2013;65: 2499–2512.

Original Version of the Topic:  

Edward Hurvitz, MD. Juvenile Idiopathic Arthritis. Publication Date:  2011/11/10.

Author Disclosure

Todd R. Lefkowitz, MD
IMEDECS – Monetary (Consultant)

Sean Bemanian, MD
Nothing to Disclose

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